In view of the growing demand for new and more effective treatments for alcohol use disorders (AUDs), which are highly prevalent in the population, a need exists for investigators with expertise in the conduct of alcohol treatment research.. There is also a need for researchers who are conversant with human genetics and in particular, pharmacogenetics, to translate these rapidly evolving fields into meaningful advances in the treatment of patients with AUDs. I propose a four-year plan of mentored patient-oriented research (POR) at the the NIAAA-funded Alcohol Research Center at the Univ. of CT Health Center under the supervision and mentorship of Dr. Henry Kranzler. The plan includes completion of substantial coursework and mentoring in applied statistics, with an emphasis on the application of pharmacogenetics to both the acute response to alcohol and the treatment of alcohol dependence. I will also complete coursework in translational genomics to assist me in achieving my main goal of developing an independent program of research on the application of pharmacogenetics to clinical trials for alcohol dependence by the end of the four-year career award period. I will complete a 12-week randomized, placebo-controlled clinical trial of the novel anticonvulsant zonisamide in 40 alcohol dependent subjects, which will provide me with pilot data for additional research proposals. I will also continue my work in ongoing trials and human alcohol challenge studies, all of which include pharmacogenetic components. The acquisition of new skills will be achieved through formal coursework (including the ethical conduct of research) and continued collaboration with established investigators and the ongoing receipt of mentoring in clinical trials and pharmacogenetics (to enable me to apply the skills learned in the classroom in the context of ongoing clinical research). I will also continue to develop my skills in grantsmanship, manuscript preparation, effective communication, academic collaboration, and leadership. This revised application contains substantial revisions resulting in well-focused career development and research plans, and explication of the need for further training. Receipt of this award is key to my continued development as a clinical alcohol researcher. PUBLIC HEALTH RELEVANCE: This research will focus on improving medical treatments for alcoholism, a condition that continues to be prevalent in the United States, and is a major public health concern. This research will provide for the training and development of a medical scientist who will specialize in developing state of the art medical interventions to improve treatment and outcomes for patients with alcoholism.